Early diagnosis and successful long-term management of a rare, severe lysosomal acid lipase deficiency/Wolman disease patient: Infancy to age five.

Background: This report describes a unique case of long-term survival of a young girl who was diagnosed with severe, rapidly progressive lysosomal acid lipase deficiency (LAL-D; historically "Wolman disease") at three months of age and began receiving therapeutic interventions at four months of age. This disease involves rapidly progressive multisystemic impairments and limited survival (6-12 months) without treatment.

Methods: Case report taking into account clinical aspects and patient management including a semi-structured interview with the main family caregiver.

Impact of discontinuing 5 years of enzyme replacement treatment in a cohort of 6 adults with hypophosphatasia: A case series.

Asfotase alfa is a human recombinant enzyme replacement therapy for hypophosphatasia. We describe 6 adults who were treated with asfotase alfa for 61-68 months in a clinical trial (NCT01163149), after which asfotase alfa was discontinued for 15-48 months. The patients experienced clinical deterioration and, when treatment was restarted, showed improvement.

Clinical Characteristics and Outcome of Canadian Patients Diagnosed With Atypical Hemolytic Uremic Syndrome.

Background: Atypical hemolytic uremic syndrome (aHUS) is an extremely rare, heterogeneous disease of uncontrolled activation of the alternative complement pathway that is difficult to diagnose. We have evaluated the Canadian patients enrolled in the Global aHUS Registry to provide a Canadian perspective regarding the diagnosis and management of aHUS and the specific challenges faced.

Objective: To evaluate Canadian patients enrolled in the Global aHUS Registry to provide a Canadian perspective regarding the diagnosis and management of aHUS and the specific challenges faced.

Exploiting the vitamin B12 pathway to enhance oral drug delivery via polymeric micelles.

Vitamin B12 (VB12)-modified dextran-g-polyethyleneoxide cetyl ether (DEX-g-PEO-C16) was synthesized by linking VB12 residues to a DEX-g-PEO-C16 copolymer via a 2,2'-(ethylenedioxy)bis(ethylamine) spacer. The level of VB12 substitution on the DEX-g-PEO-C16 copolymer reached 1.68% (w/w).

Engineering polysaccharide-based polymeric micelles to enhance permeability of cyclosporin A across Caco-2 cells.

Purpose: To assess and compare the effectiveness of two types of polysaccharide-based micelles as delivery vehicles for poorly water soluble drugs by monitoring their permeability across Caco-2 cell monolayers.

Methods: Dextran (DEX) and hydroxypropylcellulose (HPC) were hydrophobically modified (HM) by grafting polyoxyethylene cetyl ether (POE-C16, 15 mol% and 5.4 mol%, respectively).

Solubilization of poorly water soluble drugs in micelles of hydrophobically modified hydroxypropylcellulose copolymers.

The main objective of this study is to exploit the solubilizing potential of hydroxypropylcellulose-g-polyoxyethylene alkyl ether (HPC-g-(POE)(y)-C(n)) polymeric micelles towards poorly water soluble drugs in order to improve their oral bioavailability. Hydrophobically modified HPC graft copolymers of various compositions were synthesized by attaching hexadecyl or octadecyl residues to the hydrophilic HPC backbone via short POE linkers of different lengths. The onset of micellization was estimated by fluorescence spectroscopy.

Solubilization of cyclosporin A in dextran-g-polyethyleneglycolalkyl ether polymeric micelles.

Solubilization of the poorly water-soluble drug, Cyclosporin A (CsA), in aqueous dispersions of dextran-grafted-polyethyleneglycolalkyl ether (DEX-g-PEG-Cn) polymeric micelles was examined as a function of copolymer structure. In aqueous solution, DEX-g-PEG-Cn form polymeric micelles of low critical association concentrations (CAC) and small micelle sizes as determined by fluorescence spectroscopy and dynamic light scattering (DLS). Copolymers with longer polysaccharide chain showed larger CAC and mean diameter.

Polymer based pH-sensitive carriers as a means to improve the cytoplasmic delivery of drugs.

pH-sensitive niosomal and liposomal formulations bearing alkylated N-isopropylacrylamide (NIPAM) copolymers were characterized with regard to vesicle-polymer interaction, pH-responsiveness and stability in human serum. The interactions between the pH-sensitive NIPAM copolymer and the vesicles were studied by spectrofluorimetry, using covalently-attached pyrene as a probe. In contrast to liposomes, where complexation of copolymer to the lipid bilayer is essentially mediated by hydrophobic interactions, the binding between niosomes and PNIPAM was mainly driven by hydrogen bonding.

Preparation and tumor cell uptake of poly(N-isopropylacrylamide) folate conjugates.

Folate conjugates (PNIPAM-NH-FA) of a copolymer of N-isopropylacrylamide (NIPAM) and amino-N'-ethylenedioxy-bis(ethylacrylamide) were prepared by an efficient synthesis leading to random grafting, via a short dioxyethylene spacer, of approximately 7 folic acid residues per macromolecule. The chemical composition of the copolymer was characterized by (1)H NMR and UV/vis spectroscopy. A fluorophore-labeled folate PNIPAM conjugate was tested by in vitro assays performed with cultured KB-31 cells overexpressing the folate receptor.